Pharmacokinetics of Cannabis and its Secondary Metabolites

Once Cannabis enters the body, it undergoes a variety of different biological pathways that allow for its therapeutic effects to arise. In order to gain a better understanding of how Cannabis can be efficiently used for medicinal purposes, it is imperative to investigate its pharmacokinetic properties following consumption.

Cannabis can be ingested in various forms. This picture shows a cannabis smoothie.
Image Credit: Elvira Koneva/Shutterstock.com

The Compounds of Cannabis

The three main species typically recognized within the Cannabis sativa L. family include Cannabis sativa, Cannabis indica, and Cannabis ruderalis. Currently, it is estimated that over 545 compounds are present within the Cannabis plant, which include:

  • Phytocannabinoids
  • Alkanes
  • Sugars
  • Nitrogenous compounds
  • Flavonoids
  • Non-cannabinoid phenols
  • Phenylpropanoids
  • Steroids
  • Fatty acids
  • Terpenes

The most well-known and widely documented compounds within the Cannabis plant include trans-Δ-9-tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN). Despite the common cannabinoid origin that these three ingredients possess, they differ greatly in their pharmacological activity.

THC, for example, is often used to treat nausea and vomiting in patients receiving chemotherapy, whereas CBD is associated with a variety of different health benefits.

While there remains a lack of understanding behind the mechanisms associated with the therapeutic benefits of Cannabis compounds, many researchers are growing increasingly interested in evaluating these compounds, as well as their secondary metabolites, for a variety of clinical applications.

The Pharmacokinetics of Cannabis Compounds

It is widely accepted that the route of Cannabis administration plays a direct role in determining its efficacy towards certain conditions. For example, the consumption of Cannabis through the respiratory tract, which is primarily achieved through smoking, can allow for rapid and efficient delivery of Cannabis compounds for both therapeutic and recreational purposes.

Other ways in which Cannabis can be consumed is through oral ingestion, such as through capsules, food or drink products that have been infused with this plant, as well as dermal, rectal, or ophthalmic routes of administration; however, the latter two routes are less common.

Once Cannabis enters the body, it is rapidly distributed from the blood plasma to other tissues. While the absorption of Cannabis can vary between individuals, its compounds can be primarily found in the brain, lung, heart, and liver. Cannabis is an extremely lipophilic drug; therefore, its affinity towards adipose tissue often leads to its accumulation in this location in chronic users.

Once Cannabis compounds enter the liver, it begins to metabolize into a variety of different compounds by primarily cytochrome P450 (CYP) complex enzymes. Other organs that express CYP enzymes, such as the brain, small intestine, heart and lung are also capable of metabolizing Cannabis following absorption. Once metabolized, cannabinoids are excreted from the body as carboxylate, hydroxylate and acid metabolites.

Effects of Cannabis Consumption

After being smoked, the most common symptom associated with Cannabis consumption includes euphoria, which encompasses the sensations of relaxation and pleasure that are typically associated with the “high.” Other side effects of Cannabis smoking can include memory and cognitive effects, altered motor and psychomotor function, as well as delayed reaction time.

Cannabis plant
Image Credit: Oleksandrum/Shutterstock.com

Is Cannabis Toxic?

To date, there is no data supporting any acute toxicity following Cannabis consumption, aside from some coma situations that have occurred when this plant had been ingested by children. When considering the possible chronic toxicity of Cannabis, each organ system must be considered separately.

For example, the smoking of Cannabis can alter oxygen delivery and increase blood pressure, thereby increasing the likelihood of adverse effects to occur in patients with hypertension or other cardiovascular diseases. Respiratory complications such as bronchitis, emphysema and lung cancer can also arise in chronic Cannabis smokers.

Like many other drugs, it has been confirmed that Cannabis users can experience dependence and even withdrawal symptoms following its use. Some of the common effects associated with the withdrawal syndrome of Cannabis include anxiety, irritability, insomnia, muscle tremor, anorexia and increased reflexes.

Sources

  • Goncalves, J., Rosado, T., Soares, S., Simao, A. Y., Caramelo, D., Luis, A., et al. (2019). Cannabis and Its Secondary Metabolites: Their Use as Therapeutic Drugs, Toxicological Aspecs, and Analytical Determination. Medicines 6(1); 31. DOI: 10.3390/medicines6010031.

Further Reading

Last Updated: Feb 3, 2021

Benedette Cuffari

Written by

Benedette Cuffari

After completing her Bachelor of Science in Toxicology with two minors in Spanish and Chemistry in 2016, Benedette continued her studies to complete her Master of Science in Toxicology in May of 2018. During graduate school, Benedette investigated the dermatotoxicity of mechlorethamine and bendamustine; two nitrogen mustard alkylating agents that are used in anticancer therapy.

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